Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired Staphylococcus aureus Infections.
Veronica FollieroFederica Dell'AnnunziataBiagio SantellaEmanuela RoscettoCarla ZannellaNicoletta CapuanoAlessandro PerrellaAnna De FilippisGiovanni BocciaMaria Rosaria CataniaMassimiliano GaldieroGianluigi FranciPublished in: Microorganisms (2023)
The emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth at 6.3 μg/mL concentrations against reference gram-positive strains, while no antibacterial activity was found against gram-negative strains up to the highest concentration tested of 50 μg/mL. Given its relevance as a community and hospital pathogen, further studies have been performed on selamectin activity against Staphylococcus aureus ( S. aureus ), using clinical isolates with different antibiotic resistance profiles and a reference biofilm-producing strain. Antibacterial studies have been extensive on clinical S. aureus isolates with different antibiotic resistance profiles. Mean MIC 90 values of 6.2 μg/mL were reported for all tested S. aureus strains, except for the macrolide-resistant isolate with constitutive macrolide-lincosamide-streptogramin B resistance phenotype (MIC 90 9.9 μg/mL). Scanning Electron Microscopy (SEM) showed that selamectin exposure caused relevant cell surface alterations. A synergistic effect was observed between ampicillin and selamectin, dictated by an FIC value of 0.5 against methicillin-resistant strain. Drug administration at MIC concentration reduced the intracellular bacterial load by 81.3%. The effect on preformed biofilm was investigated via crystal violet and confocal laser scanning microscopy. Selamectin reduced the biofilm biomass in a dose-dependent manner with minimal biofilm eradication concentrations inducing a 50% eradication (MBEC 50 ) at 5.89 μg/mL. The cytotoxic tests indicated that selamectin exhibited no relevant hemolytic and cytotoxic activity at active concentrations. These data suggest that selamectin may represent a timely and promising macrocyclic lactone for the treatment of S. aureus infections.
Keyphrases
- gram negative
- staphylococcus aureus
- multidrug resistant
- electron microscopy
- escherichia coli
- biofilm formation
- drug resistant
- acinetobacter baumannii
- pseudomonas aeruginosa
- methicillin resistant staphylococcus aureus
- candida albicans
- silver nanoparticles
- healthcare
- high resolution
- cell surface
- drug administration
- helicobacter pylori infection
- adverse drug
- small molecule
- mental health
- single cell
- anti inflammatory
- mass spectrometry
- acute care
- high speed
- atomic force microscopy
- machine learning
- replacement therapy
- electronic health record
- reactive oxygen species